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Blood, 15 December 2005, Vol. 106, No. 13, pp. 4057-4065.
Prepublished online as a Blood First Edition Paper on August 23, 2005; DOI 10.1182/blood-2005-03-1004.


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Submitted March 15, 2005
Accepted August 11, 2005

Allogeneic marrow stromal cells are immune rejected by MHC class I and II mismatched recipient mice

Nicoletta Eliopoulos, John Stagg, Laurence Lejeune, Sandra Pommey, and Jacques Galipeau*

Lady Davis Institute for Medical Research, McGill University, Montreal, Quebec, Canada
Lady Davis Institute for Medical Research, McGill University, Montreal, Quebec, Canada; Division of Hematology/Oncology, Jewish General Hospital, McGill University, Montreal, Quebec, Canada

* Corresponding author; email: jacques.galipeau{at}mcgill.ca.

It has been suggested that marrow stromal cells (MSCs) may be immunoprivileged and can engraft in allogeneic recipients with intact immune systems. We determined if the implantation of murine MSCs engineered to release erythropoietin (Epo) would be feasible in MHC-mismatched allogeneic mice without immunosuppression and we monitored hematocrit (Hct) as a reporter of MSC graft survival. MSCs from C57Bl/6 mice were engineered to release murine Epo (Epo+MSCs) and implanted subcutaneously in either syngeneic C57Bl/6 mice or MHC mismatched Balb/c mice. In syngeneic recipients, the Hct rapidly rose from baseline level and remained >88% for >200 days. However, in MHC-mismatched recipient Balb/c mice, the Hct rose transiently and rapidly declined to baseline values. Repeat implantations in these same mice were associated with an acquired refractoriness in the Hct response consistent with alloimmunization to donor Epo+MSCs. Allogeneic MSC implants had an increased proportion of host-derived lymphoid CD8+, NK T, and NK infiltrating cells compared with syngeneic controls, and splenocytes isolated from implanted Balb/c mice also displayed a significant IFN{gamma} response to C57Bl/6 MSCs in vitro. These results strongly suggest that MSCs are not intrinsically immunoprivileged and cannot serve as a "universal donor" in immunocompetent MHC mismatched recipients.


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